Expanding into new markets – VCP/p97 in endocytosis and autophagy

Bug, Monika; Meyer, Hemmo

doi:10.1016/j.jsb.2012.03.003

Cited by 82 publications

(74 citation statements)

References 65 publications

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“…Recently, VCP was demonstrated to be also involved in autophagic degradation of ubiquitinated substrates [26,27]. To evaluate whether autophagy-mediated protein degradation, similar to UPS-mediated degradation, is impaired by the loss of Vcp in vivo , we assessed protein levels of Sqstm1/p62 (sequestosome 1) and Lc3A/B-II, the lipidated and autophagosome-associated form of Lc3A/B or Map1lc3A/B (microtubule-associated protein 1 light chain 3) (hereafter referred to as Lc3), 2 established markers of autophagy function [28].…”

Section: Resultsmentioning

confidence: 99%

Loss of the novel Vcp (valosin containing protein) interactor Washc4 interferes with autophagy-mediated proteostasis in striated muscle and leads to myopathy in vivo

et al. 2018

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VCP/p97 (valosin containing protein) is a key regulator of cellular proteostasis. It orchestrates protein turnover and quality control in vivo, processes fundamental for proper cell function. In humans, mutations in VCP lead to severe myo- and neuro-degenerative disorders such as inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD), amyotrophic lateral sclerosis (ALS) or and hereditary spastic paraplegia (HSP). We analyzed here the in vivo role of Vcp and its novel interactor Washc4/Swip (WASH complex subunit 4) in the vertebrate model zebrafish (Danio rerio). We found that targeted inactivation of either Vcp or Washc4, led to progressive impairment of cardiac and skeletal muscle function, structure and cytoarchitecture without interfering with the differentiation of both organ systems. Notably, loss of Vcp resulted in compromised protein degradation via the proteasome and the macroautophagy/autophagy machinery, whereas Washc4 deficiency did not affect the function of the ubiquitin-proteasome system (UPS) but caused ER stress and interfered with autophagy function in vivo. In summary, our findings provide novel insights into the in vivo functions of Vcp and its novel interactor Washc4 and their particular and distinct roles during proteostasis in striated muscle cells.

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Section: Resultsmentioning

confidence: 99%

Loss of the novel Vcp (valosin containing protein) interactor Washc4 interferes with autophagy-mediated proteostasis in striated muscle and leads to myopathy in vivo

et al. 2018

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“…Examples include dissociation of protein complexes or extraction of proteins from membrane surfaces. In doing so, p97 can facilitate membrane trafficking, protein complex remodeling, and proteasomal protein degradation (19,20,23).…”

Section: Resultsmentioning

confidence: 99%

Degradation of the Deubiquitinating Enzyme USP33 Is Mediated by p97 and the Ubiquitin Ligase HERC2

Chan

Besten

Sweredoski

et al. 2014

Journal of Biological Chemistry

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“…evidence connects VCP/p97 to lysosomal protein degradation through its ability to facilitate cargo sorting through the endosomal pathway as well as autophagy (Ju and Weihl, 2010;Bug and Meyer, 2012). The underlying mechanisms, particularly in autophagy, are still unclear or controversial (Ju and Weihl, 2010;Bug and Meyer, 2012).…”

Section: Box 1 Mechanisms Of Ubiquitylation and Links To Vcp/ P97mentioning

confidence: 99%

“…The underlying mechanisms, particularly in autophagy, are still unclear or controversial (Ju and Weihl, 2010;Bug and Meyer, 2012). However, the evidence supporting it is substantial and suggests a major relevance for VCP/p97-associated disease (see below).…”

Section: Box 1 Mechanisms Of Ubiquitylation and Links To Vcp/ P97mentioning

confidence: 99%

The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis

Meyer

Weihl

2014

Journal of Cell Science

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363

421

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The ATPase valosin-containing protein (VCP)/p97 has emerged as a central and important element of the ubiquitin system. Together with a network of cofactors, it regulates an ever-expanding range of processes that stretch into almost every aspect of cellular physiology. Its main role in proteostasis and key functions in signaling pathways are of relevance to degenerative diseases and genomic stability. In this Cell Science at a Glance and the accompanying poster, we give a brief overview of this complex system. In addition, we discuss the pathogenic basis for VCP/p97-associated diseases and then highlight in more detail new exciting links to the translational stress response and RNA biology that further underscore the significance of the VCP/p97 system.

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Expanding into new markets – VCP/p97 in endocytosis and autophagy

Cited by 82 publications

References 65 publications

Loss of the novel Vcp (valosin containing protein) interactor Washc4 interferes with autophagy-mediated proteostasis in striated muscle and leads to myopathy in vivo

Loss of the novel Vcp (valosin containing protein) interactor Washc4 interferes with autophagy-mediated proteostasis in striated muscle and leads to myopathy in vivo

Degradation of the Deubiquitinating Enzyme USP33 Is Mediated by p97 and the Ubiquitin Ligase HERC2

The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis

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